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LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity.

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posted on 2023-06-09, 13:12 authored by Rhys MorganRhys Morgan, E Mortensson, D N Legge, B Gupta, T J Collard, A Greenhough, A C Williams
BACKGROUND LGR5 serves as a co-receptor for Wnt/ß-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5 cells are known to exist outside the stem cell niche during CRC progression, and the requirement for epidermal growth factor (EGF) signalling within early adenomas remains to be fully elucidated. METHODS Epidermal growth factor and gefitinib treatments were performed in EGF-responsive LGR5 early adenoma RG/C2 cells. 2D growth assays were measured using an IncuCyte. LGR5 or MEK1/2 silencing studies were executed using siRNA and LGR5 expression was assessed by qRT-PCR and immunoblotting. Ki67 level and cell cycle status were analysed by flow cytometry. RESULTS Epidermal growth factor suppresses expression of LGR5 at both the transcript and protein level in colorectal adenoma and carcinoma cells. Suppression of LGR5 reduces the survival of EGF-treated adenoma cells by increasing detached cell yield but also inducing a proliferative state, as evidenced by elevated Ki67 level and enhanced cell cycle progression. Repression of LGR5 further increases the sensitivity of adenoma cells to EGFR inhibition. CONCLUSIONS LGR5 has an important role in the EGF-mediated survival and proliferation of early adenoma cells and could have clinical utility in predicting response of CRC patients to EGFR therapy.

History

Publication status

  • Published

File Version

  • Published version

Journal

British Journal of Cancer

ISSN

1532-1827

Publisher

Nature Publishing Group

Issue

4

Volume

118

Page range

558-565

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-05-10

First Open Access (FOA) Date

2018-05-10

First Compliant Deposit (FCD) Date

2018-05-09

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